A step forward for the understanding and modulation of Parkinson’s disease
A major feature of neurological disorders, such as Parkinson’s disease, is chronic inflammation where microglia play an important role. However, the current midbrain organoid systems derived from neuro epithelial stem cells lack immune cells (microglia) thereby presenting a major limitation for the understanding of the physiological brain pathology and the development of new therapies.
Midbrain‐microglia assembloids are the first 3D in vitro models of Parkinson’s disease that integrate functional human iPSC‐derived microglia into midbrain organoids produced from neural epithelial stem cells. Microglia integration into human midbrain organoids leads to increased neuronal maturation and functionality:
Microglia within assembloids express phagocytosis related genes and release cytokines and chemokines, demonstrating relevant cellular communication abilities.
Microglia communicate with neurons and play a role in midbrain organoid stress response: assembloids display a reduction of cell death and oxidative stress‐related genes in the system, compared with midbrain organoids without microglia.
Microglia induce alterations in synaptic gene expression in assembloids and lead to increased electrophysiology properties in neurons.
- Sabate-Soler et al. (2022) Glia 70:1267. Microglia integration into human midbrain organoids leads to increased neuronal maturation and functionality
- Smits et al. (2019) npj Parkinson’s Disease 5. Modeling Parkinson’s disease in midbrain-like organoids
- Monzel et al. (2017) Stem Cell Reports 8: 1144. Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells
- Efficient and reproducible method to integrate microglia into midbrain organoids
- Enable to study reactive microgliosis and neuroinflammation in Parkinson’s disease
- Personalized approach: patient‐specific assembloids
Midbrain‐microglia assembloids models open doors to studies of neuroinflammation related pathways and, to new therapeutic targets for compounds that focus on the immune system in Parkinson’s disease.
- “Means and methods for generating midbrain organoids” Appl. No EP16785272; US15766779; JP2018517798 Owned by the University of Luxembourg and filed in 2016
- “Means and methods for generating immunocompetent midbrain assembloid” Appl. No LU500789 Owned by the University of Luxembourg and filed in 2021
- Patent application submitted